a1 Oxford University Clinical Research Unit, Vietnam
a2 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, UK
a3 Eijkman Institute for Molecular Biology, Jakarta, Indonesia
a4 Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok
a5 National Institute for Hygiene and Epidemiology, Hanoi, Vietnam
a6 Chinese Centre for Disease Control and Prevention, Beijing, People's Republic of China
a7 Genome Institute of Singapore, Genome Building, Singapore
SUMMARY
The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.
(Accepted February 10 2010)
(Online publication March 18 2010)
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c1 Author for correspondence: Dr P. Horby, Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford OX3 7LJ, UK. (Email: peter.horby@gmail.com)